Disease-Dependent Antiapoptotic Effects of Cannabidiol for Keratinocytes Observed upon UV Irradiation
Although apoptosis of keratinocytes has been relatively well studied, there is a lack of information comparing potentially proapoptotic treatments for healthy and diseased skin cells. Psoriasis is a chronic autoimmune-mediated skin disease manifested by patches of hyperproliferative keratinocytes th...
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/18/9956 |
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| author | Piotr Wójcik Agnieszka Gęgotek Neven Žarković Elżbieta Skrzydlewska |
| author_facet | Piotr Wójcik Agnieszka Gęgotek Neven Žarković Elżbieta Skrzydlewska |
| author_sort | Piotr Wójcik |
| collection | DOAJ |
| description | Although apoptosis of keratinocytes has been relatively well studied, there is a lack of information comparing potentially proapoptotic treatments for healthy and diseased skin cells. Psoriasis is a chronic autoimmune-mediated skin disease manifested by patches of hyperproliferative keratinocytes that do not undergo apoptosis. UVB phototherapy is commonly used to treat psoriasis, although this has undesirable side effects, and is often combined with anti-inflammatory compounds. The aim of this study was to analyze if cannabidiol (CBD), a phytocannabinoid that has anti-inflammatory and antioxidant properties, may modify the proapoptotic effects of UVB irradiation in vitro by influencing apoptotic signaling pathways in donor psoriatic and healthy human keratinocytes obtained from the skin of five volunteers in each group. While CBD alone did not have any major effects on keratinocytes, the UVB treatment activated the extrinsic apoptotic pathway, with enhanced caspase 8 expression in both healthy and psoriatic keratinocytes. However, endoplasmic reticulum (ER) stress, characterized by increased expression of caspase 2, was observed in psoriatic cells after UVB irradiation. Furthermore, decreased p-AKT expression combined with increased 15-d-PGJ<sub>2</sub> level and p-p38 expression was observed in psoriatic keratinocytes, which may promote both apoptosis and necrosis. Application of CBD partially attenuated these effects of UVB irradiation both in healthy and psoriatic keratinocytes, reducing the levels of 15-d-PGJ<sub>2</sub>, p-p38 and caspase 8 while increasing Bcl2 expression. However, CBD increased p-AKT only in UVB-treated healthy cells. Therefore, the reduction of apoptotic signaling pathways by CBD, observed mainly in healthy keratinocytes, suggests the need for further research into the possible beneficial effects of CBD. |
| first_indexed | 2024-03-10T07:35:54Z |
| format | Article |
| id | doaj.art-943246d0a8b44e13bf8c49d85bc67353 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T07:35:54Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-943246d0a8b44e13bf8c49d85bc673532023-11-22T13:30:14ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-012218995610.3390/ijms22189956Disease-Dependent Antiapoptotic Effects of Cannabidiol for Keratinocytes Observed upon UV IrradiationPiotr Wójcik0Agnieszka Gęgotek1Neven Žarković2Elżbieta Skrzydlewska3Department of Analytical Chemistry, Medical University of Bialystok, 15-222 Bialystok, PolandDepartment of Analytical Chemistry, Medical University of Bialystok, 15-222 Bialystok, PolandLabOS, Rudjer Boskovic Institute, 10000 Zagreb, CroatiaDepartment of Analytical Chemistry, Medical University of Bialystok, 15-222 Bialystok, PolandAlthough apoptosis of keratinocytes has been relatively well studied, there is a lack of information comparing potentially proapoptotic treatments for healthy and diseased skin cells. Psoriasis is a chronic autoimmune-mediated skin disease manifested by patches of hyperproliferative keratinocytes that do not undergo apoptosis. UVB phototherapy is commonly used to treat psoriasis, although this has undesirable side effects, and is often combined with anti-inflammatory compounds. The aim of this study was to analyze if cannabidiol (CBD), a phytocannabinoid that has anti-inflammatory and antioxidant properties, may modify the proapoptotic effects of UVB irradiation in vitro by influencing apoptotic signaling pathways in donor psoriatic and healthy human keratinocytes obtained from the skin of five volunteers in each group. While CBD alone did not have any major effects on keratinocytes, the UVB treatment activated the extrinsic apoptotic pathway, with enhanced caspase 8 expression in both healthy and psoriatic keratinocytes. However, endoplasmic reticulum (ER) stress, characterized by increased expression of caspase 2, was observed in psoriatic cells after UVB irradiation. Furthermore, decreased p-AKT expression combined with increased 15-d-PGJ<sub>2</sub> level and p-p38 expression was observed in psoriatic keratinocytes, which may promote both apoptosis and necrosis. Application of CBD partially attenuated these effects of UVB irradiation both in healthy and psoriatic keratinocytes, reducing the levels of 15-d-PGJ<sub>2</sub>, p-p38 and caspase 8 while increasing Bcl2 expression. However, CBD increased p-AKT only in UVB-treated healthy cells. Therefore, the reduction of apoptotic signaling pathways by CBD, observed mainly in healthy keratinocytes, suggests the need for further research into the possible beneficial effects of CBD.https://www.mdpi.com/1422-0067/22/18/9956CBDskin inflammationUVBkeratinocytesapoptosis |
| spellingShingle | Piotr Wójcik Agnieszka Gęgotek Neven Žarković Elżbieta Skrzydlewska Disease-Dependent Antiapoptotic Effects of Cannabidiol for Keratinocytes Observed upon UV Irradiation International Journal of Molecular Sciences CBD skin inflammation UVB keratinocytes apoptosis |
| title | Disease-Dependent Antiapoptotic Effects of Cannabidiol for Keratinocytes Observed upon UV Irradiation |
| title_full | Disease-Dependent Antiapoptotic Effects of Cannabidiol for Keratinocytes Observed upon UV Irradiation |
| title_fullStr | Disease-Dependent Antiapoptotic Effects of Cannabidiol for Keratinocytes Observed upon UV Irradiation |
| title_full_unstemmed | Disease-Dependent Antiapoptotic Effects of Cannabidiol for Keratinocytes Observed upon UV Irradiation |
| title_short | Disease-Dependent Antiapoptotic Effects of Cannabidiol for Keratinocytes Observed upon UV Irradiation |
| title_sort | disease dependent antiapoptotic effects of cannabidiol for keratinocytes observed upon uv irradiation |
| topic | CBD skin inflammation UVB keratinocytes apoptosis |
| url | https://www.mdpi.com/1422-0067/22/18/9956 |
| work_keys_str_mv | AT piotrwojcik diseasedependentantiapoptoticeffectsofcannabidiolforkeratinocytesobserveduponuvirradiation AT agnieszkagegotek diseasedependentantiapoptoticeffectsofcannabidiolforkeratinocytesobserveduponuvirradiation AT nevenzarkovic diseasedependentantiapoptoticeffectsofcannabidiolforkeratinocytesobserveduponuvirradiation AT elzbietaskrzydlewska diseasedependentantiapoptoticeffectsofcannabidiolforkeratinocytesobserveduponuvirradiation |